Deletion/insertion mutation of Wilson disease (WD) gene in 16 Japanese patients with Wilson disease was studied. A truncated size in a region of exon 4 to 6 was found by reverse transcription-polymerase chain reaction (RT-PCR) covering entire 21 exons except exon 1 for liver cDNA of one patient with a late onset neurologic type. Sequence analysis of the cDNA revealed that this truncation was occurred by skipping of exon 5, though any mutation in exon 5 of genomic DNA was failed to detect. T to G transversion in 5 bp upstream from a junction of intron 4 and exon 5 was found in genomic DNA of the patient. Further, results obtained by RT-PCR and the sequence analysis in intron 4 indicate that the mutation of the patient is homozygous. Since same mutation in one allele of another patient out of 15 patients was found, allele frequency of the splicing mutation in Japanese patients is 9.4%. These results suggest that the point mutation in intron 4 of WD gene causes the skipping of exon 5 and the splicing mutation affects the phenotype of Wilson disease.